The primary objective of human islet transplantation into patients with Type I, Insulin Dependent Diabetes Mellitus (IDDM) is to determine whether the transplantation of isolated, purified, adult human islets can eliminate the need for insulin therapy. Recent improvements in the methods of isolation and purification of human islets from cadaver donated human pancreas have provided consistently high yields of 70-95% pure human islets that contain 50-100 units of insulin. These islets respond appropriately to a glucose challenge in vitro and can be successfully transplanted into nude mice. It has also been demonstrated that human islets remain viable after seven days of culture at room temperature which may reduce their potential for rejection. Thus, a markedly improved human islet preparation is now available to test in patients with Type I IDDM. This application proposes to (1) transplant under local anesthesia, room temperature-cultured islets into the portal vein of patients with type I IDDM who have had their disease for 20 years and have minimal complications. These patients will receive prednisone, azathioprine and cyclosporine for 12 months. All patients off insulin at that time will have their immunosuppression removed to determine whether the combination of transient immunosuppression and low temperature culture will permit long term engraftment of the altered islets as has been shown in animal studies. It proposed to (2) transplant purified human islets via the portal view into Type I IDDM patients who have already received a kidney transplant and are on basal immunosuppression. The renal subcapsular site will also be examined by transplanting 2 day cultured islets from the same donor as a kidney allograft. The third study will be to (3) transplant cryopreserved human islets to determine the feasibility of islet banking human islets for future clinical trials. The results of these proposed studies of transplanting purified human islets into different groups of patients with diabetes should determine the potential of considering islet transplantation as a method for clinical treatment of patients with Type I IDDM.